What is the difference between Tnkase (tenecteplase) and tPA (alteplase) in the management of acute ischemic stroke?

Tenecteplase vs Alteplase for Acute Ischemic Stroke

Tenecteplase (0.25 mg/kg as a single bolus) is a suitable alternative to alteplase (0.9 mg/kg over 60 minutes) for acute ischemic stroke within 4.5 hours of symptom onset, with equivalent functional outcomes and safety, while offering significant practical advantages through single-bolus administration. 1, 2

Key Pharmacologic Differences

Tenecteplase is a genetically engineered variant of alteplase with superior pharmacologic properties:

• Longer half-life: 90-130 minutes compared to alteplase's shorter duration, allowing single-bolus administration rather than a 1-hour infusion 1, 3
• Higher fibrin specificity: Results in more targeted clot dissolution with potentially lower systemic bleeding risk 4, 3
• Single-bolus dosing: Administered as one weight-based IV push versus alteplase's 10% bolus followed by 90% infusion over 60 minutes 1, 3

Dosing Protocols

Tenecteplase dosing for stroke:

• 0.25 mg/kg as a single IV bolus (maximum 25 mg) 1, 3
• Weight-based tiers: 30 mg for <60 kg, 35 mg for 60-69 kg 1
• Critical caveat: Do not confuse with myocardial infarction dosing (0.5 mg/kg), which is different 1

Alteplase dosing:

• 0.9 mg/kg (maximum 90 mg total) 5, 6
• 10% as IV bolus over 1 minute, remaining 90% infused over 60 minutes 5, 1

Clinical Efficacy Evidence

The ORIGINAL trial (2024) provides the highest quality comparative data:

• Tenecteplase achieved excellent functional outcomes (mRS 0-1) in 72.7% versus alteplase 70.3% (RR 1.03,95% CI 0.97-1.09), meeting noninferiority criteria 2
• Symptomatic intracranial hemorrhage rates were identical: 1.2% in both groups 2
• 90-day mortality: 4.6% tenecteplase versus 5.8% alteplase (RR 0.80) 2

Meta-analyses of 1585 randomized patients demonstrate:

• Tenecteplase shows superiority in recanalization of large vessel occlusions 3
• Noninferiority in disability-free 3-month outcomes 3
• No increase in symptomatic intracranial hemorrhage or mortality 3

Guideline Recommendations

The American Heart Association/American Stroke Association provides:

• Class IIb recommendation (Level of Evidence B-R) for tenecteplase as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion 1
• Tenecteplase "might be considered" as a second-tier option 1, 3

The Canadian Stroke Best Practices note:

• Tenecteplase achieves superior arterial recanalization prior to mechanical thrombectomy (22% vs 10% substantial reperfusion) 1
• Further evidence from ongoing trials was required before recommending widespread practice changes 1

Practical Advantages of Tenecteplase

Single-bolus administration offers significant workflow benefits:

• Reduces nursing time and potential medication errors 1
• Particularly advantageous in centers considering endovascular therapy or patient transfer 1
• Simplifies administration in time-critical situations 1

Time Window and Patient Selection

Both agents share the same time windows:

• 0-3 hours: Strong recommendation (Grade 1A for alteplase) 5, 6
• 3-4.5 hours: Conditional recommendation (Grade 2C) 5, 6
• Beyond 4.5 hours: Contraindicated (Grade 1B) 5

Optimal patient populations:

• Patients with NIHSS 5-22 show the most benefit 6
• Mild to moderate strokes (NIHSS <20) and patients <75 years have greatest potential for excellent outcomes 6
• Tenecteplase particularly recommended for large vessel occlusions based on superior recanalization 3

Shared Contraindications and Safety Considerations

Both agents are absolutely contraindicated in:

• Patients on direct oral anticoagulants (DOACs) like apixaban due to substantially elevated bleeding risk 6
• Evidence of intracranial hemorrhage 1
• Uncontrolled hypertension (>185/110 mm Hg despite treatment) 5
• Recent significant trauma or surgery 1

Shared safety profile:

• Baseline symptomatic ICH risk: 4-6% with proper dosing 5, 6
• Patients on antiplatelet therapy have 3% absolute increased risk of symptomatic ICH but can still receive either agent 5, 6
• Number needed to harm for symptomatic ICH: 17 1

Clinical Decision Algorithm

When choosing between tenecteplase and alteplase:

1. If large vessel occlusion present: Consider tenecteplase for superior recanalization rates 1, 3
2. If planning endovascular therapy or transfer: Tenecteplase offers workflow advantages through single-bolus administration 1
3. If minor stroke with no major intracranial occlusion: Either agent appropriate, with tenecteplase as reasonable alternative 1
4. If standard stroke presentation within 4.5 hours: Either agent provides equivalent outcomes; choose based on institutional protocols and practical considerations 2

Alteplase remains the gold standard with Level A evidence for 0-3 hour window, while tenecteplase represents an equivalent alternative with practical advantages. 6, 2

Post-Treatment Management

Identical for both agents:

• Monitor blood pressure every 15 minutes during and for 2 hours after treatment, then every 30 minutes for 6 hours, then hourly for 16 hours 5
• Maintain blood pressure <180/105 mm Hg 5
• Do NOT give anticoagulants or antiplatelet agents for 24 hours after thrombolytic administration 5, 6
• Administer aspirin 160-325 mg within 24-48 hours for patients not receiving anticoagulation 6

Common Pitfalls

Critical errors to avoid:

• Using myocardial infarction dosing (0.5 mg/kg) instead of stroke dosing (0.25 mg/kg) for tenecteplase 1
• Delaying door-to-needle time while deciding between agents; both should be administered within 60 minutes of arrival 1
• Administering either agent to patients on DOACs without proper reversal 6
• Exceeding maximum doses: 25 mg for tenecteplase, 90 mg for alteplase 5, 1